• Biomolecules & Therapeutics
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• v.7 no.3
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• pp.278-284
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• 1999

DK1001 is a thebain derivative, which is newly synthesized as an alkaloid analgesic. This study was designed to study effects of DK1001 on the ligands binding to the opioid receptor subtypes, and general pharmacology of DK1001. DK1001 inhibited the binding of [$^3H$]DAMGO, a selective mu-subtype agonist, to the opioid receptor of rat forebrain in a concentration-dependent manner. $EC_{50}$ of DK1001 was significantly lower than that of morphine. DK1001 inhibited the binding of 〔$^3$H〕DPDPE, a selective delta-subtype agonist concentration-dependently. DK1001(0.5 mg/kg) had no effects on behavior, body temperature, blood pressure. respiratory rate, and intestinal charcoal propulsion of mice. In addition, DK1001 did not affect on the contractilities of isolated muscle strips of aorta, ileum, and trachea of rats. These results suggest that DK1001 might be a potent analgesic without serious side effects.

• The Korean Journal of Pharmacology
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• v.2 no.1 s.2
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• pp.71-82
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• 1966

The inhibitory effect of 5-hydroxytryptamine (5-HT) on the isolated intestinal strips of the tortoise (Amyda japonica), rat, rabbit and guinea pig was investigated. 1) The strips from the middle or lower part of the tortoise intestine responded with relaxation to 5-HT $(10^{-9}{\sim}10^{-5}g/ml)$, and the magnitude of the relaxation was proportional to the dose of 5-HT. The rectal part of the tortoise intestine, in contrast, showed contraction, the magnitude of which also was proportional to the dose of 5-HT. 2) Various blocking agents such as methysergide, morphine, tetracaine, nethalide, bretylium, hexamethonium, mecamylamine and chlorisondamine, showed no selective blocking activity on the relaxant effect of 5-HT on the tortoise intestine. The inhibitory effect of isoproterenol on the tortoise intestine, however, was selectively blocked by nethalide, and the stimulatory effect of 5-HT on the rectal part of the tortoise was blocked by methysergide. 3) In the presence of 5-HT, the stimulatory effect of DMPP on the tortoise intestine was remarkably attenuated, whereas that of acetylcholine and $BaCl_2$ was little affected. In the presence of isoproterenol, the stimulatory effect of acetylcholine and $BaCl_2$ were affected, but that of DMPP was little affected. 4) Large dose of 5-HT($10^{-4}$g/ml) produced inhibitory effect on the strips from the distal part of the isolated colon of the rat, rabbit and guinea pig, when the strips had been exposed to 5-HT($10^{-4}$g/ml), methysergide or phen`oxybenzamine. 5) Bretylium, as well as nethalide, abolished or remarkably reduced, in a few cases of the experiments, the inhibitory effect of the large dose of 5-HT on the distal part of the colon, whereas morphine did not affect it. 6) The ileal strips of the guinea pig also showed relaxation, as in the colonic strips, having been exposed to the large dose of 5-HT or phenoxybenzamine. This effect, however, was not obsered in the case of the rabbit ileum. 7) The property of the action-site of 5-HT in the tortoise intestine seemd to be different from the 5-HT receptors which have been revealed by several investigators. 8) Adrenergic component seemed to be participated in the inhibitory effect of 5-HT on the colon of the rat and rabbit.

• Applied Microscopy
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• v.30 no.4
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• pp.357-365
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• 2000

Paneth cells have been suggested to contribute to the elimination of excess metals into the intestinal lumen. The purpose of this study wat to investigate the changes of the zinc pools in rats subjected to functional loading with zinc salt by mean of both light and electron microscopical autometallography (AMG). Wistar rats 4 were administrated with zinc chloride (20 mg/kg body weight) intraperitoneally dissolved in 1 ml distilled water. The control group received 1 ml saline IP. After further one hour the animals were transcardially perfused with 0.4% sodium sulphide dissolved in 0.1 M PB fellowed by 3% glutaraldehyde solution for 10 minutes. Pieces of ileum were frozen with solid $CO_2$ and sectioned on a cryostat. The sections $(20{\mu}m)$ were autometallographically developed. Sections selected for EM were reembedded on top of a blank Epon block, from which ultrathin sections (100 nm) were cut. The ultrathin sections were double stained with uranyl acetate (30 min) and lead citrate (5 min), then examined under electron microscope. Studies of comparable sections from control and zinc loaded animals with the AMG selenium method gave quite different results. The control animals demonstrated a weakly positive staining in the cytoplasm of the Paneth cells. In the electron microscope the AMG silver grains were found to be located in the cytoplasm, while the electron dense secretary granules and other cell organelles were void of staining. Few AMG grains were located at the apical surface of the Paneth cells. In sections from zinc loaded rats, the AMG grains were seen in abundance in the lumen of the Lieberkuhn crypts at light microscopic levels. At EM levels the zinc revealing silver grains were located in the cytoplasm as in the controls, but much more AMG grains were shifted into the secretary granules. Furthermore, profound AMG grains were found in the lumen of the crypts and surrounding vessels. And a few grains were seen in the endothelium. The AMG technique demonstrated a pattern of AMG grains in the Paneth cells that strongly suggests a transport of zinc ions through these cells.

• Korean Journal of Veterinary Research
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• v.37 no.2
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• pp.291-299
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• 1997

In order to establish optimal dosage schedules and withdrawal times for sulfamethazine(SMZ) in pigs, pharmacokinetic and tissue distribution experiments were conducted in pigs. For comparative purposes, tissue depletion kinetics are also studied in rats. From three pigs administered with SMZ i.v., the pharmacokinetic profile of SMZ in two pigs was adequately described by a one-compartment open model whereas that in one pig was patterned after a two-compartment open model. Volume of distribution(Vd) was 0.48~0.57 L/kg and biological half-life($t_{1/2}$) was 11.8-16.8 h. From three pigs dosed with SMZ p.o., pharmacokinetic profile was explainable with a one-compartment open model. Time to reach maximum SMZ concentration in serum (Tmax) was 2.8 h, 3.2 h and 7.5 h. Elimination half-life was 2.8-7.5 h. The descending order in concentration of SMZ was plsama > kidney > liver > lung > heart > pancreas > spleen > duodenum > ileum > brain > adipsoe tissue from three pigs sacrificed at 5h, 29h and 54h after the administration of SMZ, p.o.. The protein binding of SMZ in pigs was 55.2%($2.5{\mu}g/ml$), 71.5% ($5{\mu}g/kg$) and 71.5%($10{\mu}g/ml$). The mean systemic bioavailability (F) of SMZ p.o. was 49.1 %. Meanwhile the pharmacokinetic profile of SMZ in rats was adequately described by a one-compartment open model. Absorption of SMZ p.o. in the rat was very rapid. In conclusion, the oral optimal dosage regimen of SMZ for pigs was the initial dose of 45.7 mg/kg followed by the maintenance dose of 30.2 mg/kg for high specific pathogens to SMZ. The time to reach below the stipulated residual allowable concentration (0.1 ppm) was calculated 93 h after oral administration of 200 mg/kg recommended by manufactureres.

• Biomolecules & Therapeutics
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• v.12 no.2
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• pp.114-121
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• 2004

This study was undertaken to evaluate the general pharmacological properties of CJ-11828, an amlodipine adipate, in experimental animals and in vitro system. CJ-11828 had no effects on general behavior, motor coordination, writhing syndromes, pentetrazol-induced chemoshock and electric shock in mice at dose levels of 3,10, anti 30 mg/kg, po. But there were decrease of body temperature, prolongation of sleeping time, and inhibition of intestinal activity in mice treated with CJ-11828 at doses of 10 and 30 mg/kg, po. CJ-11828 decreased the blood pressure in coscuous fog at the dose level of 2mg/kg, po, but it was expected as a result of pharmacological activity of CJ-11828. Any effect on respiratory system was not observed in conscious rat at doses of 3,10, and 30 mg/kg, po. The slight decrease in spontaneous motor activity was observed in mice treated with CJ-11828 at high dose, 30 mg/kg. In vitro experiments, CJ-11828 had no effect on agonists-induced contraction of isolated guinea pig ileum at 0.1, 1, and 10 ${\mu}$M. Based on these results, it was concluded that CJ-11828 had no pharmacological effect ill these studies even up to the 36-fold anticipated clinical dose, 3 mg/kg.

• Toxicological Research
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• v.26 no.3
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• pp.223-232
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• 2010

Artesunate, a semi-synthetic derivative of artemisinin, is used primarily as a treatment for malaria. Its effects on the central nervous system, general behavior, and cardiovascular, respiratory, and other organ systems were studied using mice, rats, guinea pigs, and dogs. Artesunate was administered orally to mice at doses of 125, 250, and 500 mg/kg and to rats and guinea pigs at 100, 200, and 400 mg/kg. In dogs, test drugs were administered orally in gelatin capsules at doses of 50, 100, and 150 mg/kg. Artesunate induced insignificant changes in general pharmacological studies, including general behavior, motor coordination, body temperature, analgesia, convulsion modulation, blood pressure, heart rate (HR), and electrocardiogram (ECG) in dogs in vivo; respiration in guinea pigs; and gut motility or direct effects on isolated guinea pig ileum, contractile responses, and renal function. On the other hand, artesunate decreased the HR and coronary flow rate (CFR) in the rat in vitro; however, the extent of the changes was small and they were not confirmed in in vivo studies in the dog. Artesunate increased hexobarbital-induced sleeping time in a dose-related manner. Artesunate induced dose-related decreases in the volume of gastric secretions and the total acidity of gastric contents, and induced increases in pH at a dose of 400 mg/kg. However, all of these changes were observed at doses much greater than clinical therapeutic doses (2.4 mg/kg in humans, when used as an anti-malarial). Thus, it can be concluded that artesunate is safe at clinical therapeutic doses.

• Biomolecules & Therapeutics
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• v.13 no.1
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• pp.26-31
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• 2005

The present study examined effects of a water-soluble fraction from mulberry leaves (ML water fraction) on the circulatory and autonomic nervous systems, which were compared with those of acetylcholine (ACh) used as a reference drug in order to elucidate its mechanism of action. Intravenous administration of ACh or a ML water fraction produced temporary depressor and tachycardiac responses in a dose-dependent manner in unrestrained, conscious Sprague-Dawley rats. The systemic hemodynamic effects of ACh and a ML water fraction were almost completely blocked by pretreatment with atropine, a muscarinic antagonist. The depressor responses to ACh and a ML water fraction were slightly enhanced and prolonged by pretreatment with neostigmine, an anticholinesterase, whereas the tachycardiac responses were remarkably blocked by pretreatment with pentolinium, a ganglionic blocking agent. In vitro experiments using the ileum isolated from rats showed that ACh and a ML water fraction increased ileal contractility in a dose-dependent manner. The increases in ileal contractility were also completely abolished in the presence of atropine. Finally, the specific binding of [$^3H$]quinuclidinyl benzilate, a muscarinic antagonist, to rat cortical synaptic membranes was inhibited by a ML water fraction in a concentration-dependent manner with an IC$_{50}$ value of 9.5 mg/ml. The results suggest that the effects of a ML water fraction are mediated through direct stimulation of muscarinic cholinergic receptors by unknown cholinomimetic substance(s) contained in that fraction.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.4 no.1
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• pp.1-16
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• 1998

In order to investigate the effect of Bujaleejungtang, by means of oral medication to rats and mice, to isolated intestine and stomach, and the effect to pyloric ulcer, indomethacin-induced ulcer, secretion of gastric juice, and to transport ability of intestine content were studied as the action to G-I tract. The effect to normal rats and resperpine-treated rats were studied as the action to thermo-regulation. The results were as follows: 1. Bujaleejungtang showed the inhibitory effect on the smooth muscle contraction induced by acethylcholine chloride and barium chloride in the isolated mice ileum. 2. Bujaleejungtang showed inhibitory effect on the contraction induced by acetylcholine chloride and barium chloride in the rat fundus-strip. 3. Inhibitory effect of Bujaleejungtang on pyloric ulcer, indomethacin-induced gastric ulcer in rats was statistical recognized(p<0.05). 4. No inhibitory effect of Bujaleejungtang on gastric juice secretion in Shay rats was recognized. 5. Inhibitory effect of Bujaleejungtang on gastric free acidity and total acidity in Shay rats was recognized only when Bujaleejungtang was medicated in high thickness(2000mg/kg) (p<0.001). 6. Inhibitory effect of Bujaleejungtang on pepsin output in Shay rats was recognized only when Bujaleejungtang was medicated in high thickness(2000mg/kg)(p<0.001). 7. Inhibitory effect of Bujaleejungtang on barium sulfate transport in the small intestine of mice was recognized only when Bujaleejungtang was medicated in high thickness(2000mg/kg)(p<0.05). 8. Inhibitory effect of Bujaleejungtang on barium sulfate transport in the large intestine of mice was recognized(p<0.05). 9. Inhibitory effect of Bujaleejungtang on rectal temperature in normal rats was recognized. 10. Inhibitory effect of Bujaleejungtang on rectal temperature in reserpine-treated rats was recognized only when Bujaleejungtang was medicated in high thickness(2000mg/kg)(p<0.05).

• Biomolecules & Therapeutics
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• v.8 no.1
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• pp.84-92
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• 2000

This Study was conducted to assess the single dose toxicity of DA-125, a new anthracycline anti-cancer agent, in rats and mice. The Drug was administered once intravenously to both sexes of rats and mice. Then followed a 14-day period of observation. The $LD_{50}$ Values (95% confidence limit) were estimated to be 60.9 mg/kg (57.5~64.3 mg/kg) for male rats and 60.2 mg/kg (56.2~64.5 mg/kg) for female rats, and 85.8 mg/kg (81.0~90.9 mg/kg) for male mice and 84.5 mg/kg (78.2~91.9 mg/kg) for female mice. Both sexes of rats and mice given the drug revealed the clinical sign of decreased locomotor activity, emaciation, hair loss, red-dish brown urine, salivation, and watery diarrhea. In addition, body weight from the next day to the 7th day tended to be decreased slightly in rats and mice treated with DA-125. Death occurred from the next day after administration to the 12th day. Macroscopically, congestion of gastrointestinal organ, lung, and adrenal glands were found in both sexes on the dead rats and mice. Histopathological examination of dead rats manifested atrophy of spleen, hypoplasia of bone marrow, hypcplasia and necrosis of lymphocyte in thymus, atrophy of villi in small intestine (duodenum, jejunum, and ileum), hyperplasia of granular epithelium in small intestine, degeneration of germinal epithelium in testis, defer oration of tubular epithelium in kidney, and vacuolation and myolysis of myocardium in heart. Histopathological examination of dead mice revealed hypoplasia of spleen and mesenteric lymph node, local necrosis of liver, atrophy of villi in small intestine, hyperplasia of glandular epithelium in small and large intestine, degeneration of tubular in kidney, degeneration of germinal cells in testis, and slight vacuolar degeneration of myocardium in heart.

• YAKHAK HOEJI
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• v.36 no.1
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• pp.17-25
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• 1992

The general and some other pharmacological actions of growth hormone without N-terminal methionine(rhGH) were investigated in animals. The hormone had no influences on the central nervous system and on body temperature at a high oral dose of 40 IU/kg in animals. It had neither analgesic nor antiepileptic actions at the high doses. In the isolated ileum and trachea of guinea-pig and isolated stomach fundus and uterus of rat, it showed neither contractive nor relaxing effects at a concentration of $1{\times}10^{-3}\;IU/ml$ in bath, and no inhibitory action at a dose of $1{\times}10^{-3}\;IU/ml$ against the contractions produced by histamine ($5{\times}10^{-5}\;g/ml$), serotonin($1{\times}10^{-5}\;g/ml$), acetylcholine($1{\times}10^{-5}\;g/ml$) and oxytocin($5{\times}10^{-3}\;IU/ml$). Furthermore, the intravenous injection of 20 IU/kg rhGH had no influences on the normal blood pressure and respiration in rabbits. These negative results in pharmacological profile are thought that the hormone may not elicit serious side effects. On the other hand, the rhGH exhibited a weak inhibitory action of glucose tolerance in normal rats, significantly lowered the blood glucose contents in adrenalectomized rats 20 min after i.v. administration of 80 IU/kg, and showed a significant inhibitory effect on in vitro glycerol release in epinephrine-stimulated epididymal fat pad segments of rats.